rs519704

Positions:

• chr2-31580233-G-A
• chr2-31580233-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000348.4(SRD5A2):​c.281+387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,214 control chromosomes in the GnomAD database, including 1,081 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1081 hom., cov: 33)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

SRD5A2 (HGNC:11285): (steroid 5 alpha-reductase 2) This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	NM_000348.4	c.281+387C>T		intron_variant		ENST00000622030.2
SRD5A2	XM_011533072.3	c.27-46467C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2	c.281+387C>T		intron_variant		1	NM_000348.4	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17554 AN: 152096 Hom.: 1079 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17570 AN: 152214 Hom.: 1081 Cov.: 33 AF XY: 0.115 AC XY: 8528 AN XY: 74408

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0981

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0375 Hom.: 28

Bravo AF: 0.115

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.73
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs519704; hg19: chr2-31805303;